Anticancer effect and safety of doxorubicin and nutraceutical sulforaphane liposomal formulation in triple-negative breast cancer (TNBC) animal model
Female breast cancer is the most deadly cancer in women worldwide. The triple-negative breast cancer subtype therapies, due to the lack of specific drug targets, are still based on systemic chemotherapy with doxorubicin, which is burdened with severe adverse effects. To enhance therapeutic success a...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223002780 |
| _version_ | 1797857688609095680 |
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| author | Anna Pogorzelska Maciej Mazur Marta Świtalska Joanna Wietrzyk Dawid Sigorski Krzysztof Fronczyk Katarzyna Wiktorska |
| author_facet | Anna Pogorzelska Maciej Mazur Marta Świtalska Joanna Wietrzyk Dawid Sigorski Krzysztof Fronczyk Katarzyna Wiktorska |
| author_sort | Anna Pogorzelska |
| collection | DOAJ |
| description | Female breast cancer is the most deadly cancer in women worldwide. The triple-negative breast cancer subtype therapies, due to the lack of specific drug targets, are still based on systemic chemotherapy with doxorubicin, which is burdened with severe adverse effects. To enhance therapeutic success and protect against systemic toxicity, drug carriers or combination therapy are being developed. Thus, an innovative liposomal formulation containing doxorubicin and the main nutraceutical, sulforaphane, has been developed. The anticancer efficacy and safety of the proposed liposomal formulation was evaluated in vivo, in a 4T1 mouse model of triple-negative breast cancer, and the mechanism of action was determined in vitro, using triple-negative breast cancer MDA-MB-231 and non-tumorigenic breast MCF-10A cell line. The elaborated drug carriers were shown to efficiently deliver both compounds into the cancer cell and direct doxorubicin to the cell nucleus. Incorporation of sulforaphane resulted in a twofold inhibition of tumor growth and the potential of up to a fourfold reduction in doxorubicin concentration due to the synergistic interaction between the two compounds. Sulforaphane was shown to increase the accumulation of doxorubicin in the nuclei of cancer cells, accompanied by inhibition of mitosis, without affecting the reactive oxygen species status of the cell. In normal cells, an antagonistic effect resulting in less cytotoxicity was observed. In vivo results showed that sulforaphane incorporation yielded not only cardioprotective, but also nephro- and hepatoprotective effects. The results of the research revealed the prospects of applying sulforaphane as a component of liposomal doxorubicin in triple-negative breast cancer chemotherapy. |
| first_indexed | 2024-04-09T21:01:51Z |
| format | Article |
| id | doaj.art-7436444386414002955e1bdfb1625501 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-09T21:01:51Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-7436444386414002955e1bdfb16255012023-03-29T09:22:59ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-05-01161114490Anticancer effect and safety of doxorubicin and nutraceutical sulforaphane liposomal formulation in triple-negative breast cancer (TNBC) animal modelAnna Pogorzelska0Maciej Mazur1Marta Świtalska2Joanna Wietrzyk3Dawid Sigorski4Krzysztof Fronczyk5Katarzyna Wiktorska6Laboratory of Translation Research, Department of Biomedical Research, National Medicines Institute, Chełmska 30/34, Warsaw 00-725, PolandFaculty of Chemistry, University of Warsaw, Ludwika Pasteura 1, Warsaw 02-093, PolandHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, Wrocław 53-114, PolandHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, Wrocław 53-114, PolandDepartment of Oncology, Collegium Medicum, University of Warmia and Mazury, Al. Wojska Polskiego 37, Olsztyn 10-228, Poland; Department of Oncology and Immuno-Oncology, Warmian-Masurian Cancer Center of The Ministry of The Interior and Administration’s Hospital, Al. Wojska Polskiego 37, Olsztyn 10-228, PolandFaculty of Psychology, University of Warsaw, Stawki 5/7, Warsaw 00-183, PolandLaboratory of Translation Research, Department of Biomedical Research, National Medicines Institute, Chełmska 30/34, Warsaw 00-725, Poland; Corresponding author.Female breast cancer is the most deadly cancer in women worldwide. The triple-negative breast cancer subtype therapies, due to the lack of specific drug targets, are still based on systemic chemotherapy with doxorubicin, which is burdened with severe adverse effects. To enhance therapeutic success and protect against systemic toxicity, drug carriers or combination therapy are being developed. Thus, an innovative liposomal formulation containing doxorubicin and the main nutraceutical, sulforaphane, has been developed. The anticancer efficacy and safety of the proposed liposomal formulation was evaluated in vivo, in a 4T1 mouse model of triple-negative breast cancer, and the mechanism of action was determined in vitro, using triple-negative breast cancer MDA-MB-231 and non-tumorigenic breast MCF-10A cell line. The elaborated drug carriers were shown to efficiently deliver both compounds into the cancer cell and direct doxorubicin to the cell nucleus. Incorporation of sulforaphane resulted in a twofold inhibition of tumor growth and the potential of up to a fourfold reduction in doxorubicin concentration due to the synergistic interaction between the two compounds. Sulforaphane was shown to increase the accumulation of doxorubicin in the nuclei of cancer cells, accompanied by inhibition of mitosis, without affecting the reactive oxygen species status of the cell. In normal cells, an antagonistic effect resulting in less cytotoxicity was observed. In vivo results showed that sulforaphane incorporation yielded not only cardioprotective, but also nephro- and hepatoprotective effects. The results of the research revealed the prospects of applying sulforaphane as a component of liposomal doxorubicin in triple-negative breast cancer chemotherapy.http://www.sciencedirect.com/science/article/pii/S0753332223002780Triple-negative breast cancer modelsSulforaphaneDoxorubicin adverse effectsCombination therapyDrug carriersChemoprotection |
| spellingShingle | Anna Pogorzelska Maciej Mazur Marta Świtalska Joanna Wietrzyk Dawid Sigorski Krzysztof Fronczyk Katarzyna Wiktorska Anticancer effect and safety of doxorubicin and nutraceutical sulforaphane liposomal formulation in triple-negative breast cancer (TNBC) animal model Biomedicine & Pharmacotherapy Triple-negative breast cancer models Sulforaphane Doxorubicin adverse effects Combination therapy Drug carriers Chemoprotection |
| title | Anticancer effect and safety of doxorubicin and nutraceutical sulforaphane liposomal formulation in triple-negative breast cancer (TNBC) animal model |
| title_full | Anticancer effect and safety of doxorubicin and nutraceutical sulforaphane liposomal formulation in triple-negative breast cancer (TNBC) animal model |
| title_fullStr | Anticancer effect and safety of doxorubicin and nutraceutical sulforaphane liposomal formulation in triple-negative breast cancer (TNBC) animal model |
| title_full_unstemmed | Anticancer effect and safety of doxorubicin and nutraceutical sulforaphane liposomal formulation in triple-negative breast cancer (TNBC) animal model |
| title_short | Anticancer effect and safety of doxorubicin and nutraceutical sulforaphane liposomal formulation in triple-negative breast cancer (TNBC) animal model |
| title_sort | anticancer effect and safety of doxorubicin and nutraceutical sulforaphane liposomal formulation in triple negative breast cancer tnbc animal model |
| topic | Triple-negative breast cancer models Sulforaphane Doxorubicin adverse effects Combination therapy Drug carriers Chemoprotection |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223002780 |
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